Study of Fluzone® Quadrivalent, Fluzone® Intradermal Quadrivalent, and Fluzone® High-Dose, Influenza Vaccines in Adults

• ClinicalTrials.gov Identifier: NCT02563093
• Recruitment Status: Completed
• First Posted: September 29, 2015
• Results First Posted: December 12, 2016
• Last Update Posted: December 12, 2016
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

Study Description

Brief Summary:

The aim of the study is to evaluate the safety and immunogenicity of the 2015-2016 formulations of Fluzone Quadrivalent and Fluzone Intradermal Quadrivalent vaccines in adults 18 to < 65 years of age, and of the 2015-2016 formulations of Fluzone Quadrivalent and Fluzone High-Dose vaccines in adults ≥ 65 years of age.

Primary Objective:

- To describe the safety of the 2015-2016 formulations of Fluzone Quadrivalent and Fluzone Intradermal Quadrivalent vaccines in adults 18 to < 65 years of age and the safety of the 2015-2016 formulations of Fluzone Quadrivalent and Fluzone High-Dose vaccines in adults ≥ 65 years of age.

Observational Objectives:

• To describe the immunogenicity of the 2015-2016 formulations of Fluzone Quadrivalent and Fluzone Intradermal Quadrivalent vaccines in adults 18 to < 65 years of age and the immunogenicity of the 2015-2016 formulations of Fluzone Quadrivalent and Fluzone High-Dose vaccines in adults ≥ 65 years of age.
• To evaluate the compliance, in terms of immunogenicity, of each study vaccine (Fluzone Quadrivalent, Fluzone Intradermal Quadrivalent, and Fluzone High-Dose) in the applicable age group with the historical requirements of the Committee for Human Medicinal Products (CHMP) Note for Guidance (NfG) Committee for Propriety Medicinal Products (CPMP) - CHMP NfG CPMP/BWP/214/96.

Condition or disease	Intervention/treatment	Phase
Influenza	Biological: Fluzone Quadrivalent vaccine, 2015-2016 formulation, No Preservative; Biological: Fluzone Intradermal Quadrivalent vaccine, 2015-2016 formulation; Biological: Fluzone High-Dose vaccine, 2015-2016 formulation	Phase 4

Detailed Description:

Adults age 18 to < 65 years will be randomly assigned to receive either Fluzone Quadrivalent or Fluzone Intradermal Quadrivalent vaccine and adults age ≥ 65 years will be randomly assigned to receive either Fluzone Quadrivalent or Fluzone High-Dose vaccine. All subjects will receive a single dose of their randomly assigned vaccine.

They will be followed from Visit 1 to Visit 2 for evaluation of safety outcomes. Solicited adverse reactions will be collected for 7 days after vaccination. Unsolicited non-serious adverse events (AEs) and serious adverse events (SAEs) will be collected from Visit 1 to Visit 2.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 208 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Safety and Immunogenicity Among Adults of Fluzone® Quadrivalent, Fluzone® Intradermal Quadrivalent, and Fluzone® High-Dose, Influenza Vaccines, 2015-2016 Formulations
• Study Start Date: September 2015
• Actual Primary Completion Date: December 2015
• Actual Study Completion Date: July 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Study Group 1; Adults 18 to < 65 years of age randomly assigned to receive an intramuscular injection of one dose of Fluzone Quadrivalent vaccine	Biological: Fluzone Quadrivalent vaccine, 2015-2016 formulation, No Preservative; 0.5 mL, Intramuscular (IM); Other Name: Fluzone® Quadrivalent, Influenza Vaccine
Experimental: Study Group 2; Adults 18 to < 65 years of age randomly assigned to receive an intradermal injection of one dose of Fluzone Intradermal Quadrivalent vaccine	Biological: Fluzone Intradermal Quadrivalent vaccine, 2015-2016 formulation; 0.1 mL, Intradermal; Other Name: Fluzone® Intradermal Quadrivalent, Influenza Vaccine
Experimental: Study Group 3; Adults ≥ 65 years of age randomly assigned to receive an intramuscular injection of one dose of Fluzone Quadrivalent vaccine	Biological: Fluzone Quadrivalent vaccine, 2015-2016 formulation, No Preservative; 0.5 mL, Intramuscular; Other Name: Fluzone® Quadrivalent, Influenza Vaccine
Experimental: Study Group 4; Adults ≥ 65 years of age randomly assigned to receive an intramuscular injection of one dose of Fluzone High-Dose vaccine	Biological: Fluzone High-Dose vaccine, 2015-2016 formulation; 0.5 mL, Intramuscular; Other Name: Fluzone® High-Dose, Influenza Vaccine

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Solicited Injection-Site or Systemic Reactions After Receipt of the 2015-2016 Formulation of Fluzone Quadrivalent, Fluzone Intradermal Quadrivalent, or Fluzone High-Dose Vaccine [ Time Frame: Day 0 up to Day 7 post-vaccination ]

   Solicited injection-site reactions: Pain, Erythema, Swelling, Induration, and Ecchymosis. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Shivering. Grade 3 solicited injection-site reactions: Pain, Significant; prevents daily activity. Erythema, Swelling, Induration, and Ecchymosis >100 mm. Grade 3 solicited systemic reactions: Fever, ≥ 39.0°C or ≥ 102.1°F; Headache, Malaise, Myalgia, and Shivering, Significant; prevents daily activity.

   A participant (18 to < 65 Years) who was randomly assigned to receive Fluzone Intradermal Quadrivalent vaccine received Fluzone Quadrivalent vaccine instead; this participant was excluded from the Per-protocol analysis Set and was included in the Fluzone Quadrivalent vaccine Group in the Safety Analysis Set and the assigned group in the Full Analysis Set.

Secondary Outcome Measures :

1. Geometric Mean Titers of Influenza Antibodies Pre- and Post-Vaccination With the 2015-2016 Formulation of Fluzone Quadrivalent, Fluzone Intradermal Quadrivalent, or Fluzone High-Dose Vaccine [ Time Frame: Day 0 (pre-vaccination) and 21 days post-vaccination ]
   Anti-influenza antibodies were measured using an hemagglutination inhibition assay.
2. Number of Participants Achieving Seroprotection Pre and Post-Vaccination With the 2015-2016 Formulation of Fluzone Quadrivalent, Fluzone Intradermal Quadrivalent, or Fluzone High-Dose Vaccine [ Time Frame: Day 0 (Pre-vaccination) and 21 days post-vaccination ]
   Anti-influenza antibodies were measured using an hemagglutination inhibition assay. Seroprotection was defined as the number of participants with a titer ≥ 40 (1/dilution) at pre-vaccination and 21 days post-vaccination.
3. Number of Participants Achieving Seroconversion Following Vaccination With the 2015-2016 Formulation of Fluzone Quadrivalent, Fluzone Intradermal Quadrivalent, or Fluzone High-Dose Vaccine [ Time Frame: 21 days post-vaccination ]
   Anti-influenza antibodies were measured using an hemagglutination inhibition assay. Seroconversion was defined as either a pre-vaccination titer < 1:10 and a post-vaccination titer ≥ 1:40, or a pre-vaccination titer ≥ 1:10 and a ≥ 4-fold increase in titer post-vaccination.
4. Geometric Mean Titer Ratios of Influenza Antibodies Post-Vaccination With the 2015-2016 Formulation of Fluzone Quadrivalent, Fluzone Intradermal Quadrivalent, or Fluzone High-Dose Vaccine [ Time Frame: 21 days post-vaccination ]
   Anti-influenza antibodies were measured using an hemagglutination inhibition assay.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Subject is ≥ 18 years of age on the day of inclusion
• Informed consent form has been signed and dated
• Able to attend all scheduled visits and to comply with all trial procedures.

Exclusion Criteria:

• History of serious adverse reaction to any influenza vaccine
• Receipt of any vaccine within 30 days before receiving study vaccine, or plans to receive another vaccine before Visit 2
• Participation in another interventional clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 30 days preceding the first study vaccination or during the course of the study, unless no intervention for the other study occurred within the 30 days prior to the first study vaccination and none are planned before the subject would complete safety surveillance for the present study
• Thrombocytopenia, which may be a contraindication for intramuscular vaccination, at the discretion of the Investigator
• Prior vaccination with any 2015-2016 formulation of influenza vaccine
• Known systemic hypersensitivity to eggs, chicken proteins, or any of the vaccine components, or a history of a life-threatening reaction to Fluzone Quadrivalent, Fluzone Intradermal Quadrivalent, or Fluzone High-Dose vaccine or to a vaccine containing any of the same substances (the complete list of vaccine components is included in the Prescribing Information)
• Receipt of immune globulins, blood, or blood-derived products in the past 3 months
• Bleeding disorder or receipt of anticoagulants in the 3 weeks preceding inclusion, which may be a contraindication for intramuscular vaccination, at the discretion of the Investigator
• Subject is pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to vaccination and until at least 4 weeks after vaccination)
• Any condition that in the opinion of the Investigator would pose a health risk to the subject if enrolled or could interfere with the evaluation of the vaccine
• Personal history of Guillain-Barré syndrome
• Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
• Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with trial conduct or completion
• Seropositivity for human immunodeficiency virus, hepatitis B, or hepatitis C, as reported by the subject.
• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
• Current alcohol or drug addiction that, in the opinion of the Investigator, might interfere with the ability to comply with trial procedures
• Moderate or severe acute illness/infection (according to Investigator judgment) or febrile illness (temperature ≥ 100.4°F) on the day of vaccination. A prospective subject should not be included in the study until the condition has resolved or the febrile event has subsided
• Identified as an Investigator or employee of an Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of an Investigator or employee with direct involvement in the proposed study.

Contacts and Locations

Locations

United States, California

Santa Rosa, California, United States, 95405

United States, Iowa

Council Bluffs, Iowa, United States, 51503

United States, Louisiana

Metairie, Louisiana, United States, 70006

United States, Ohio

Cincinnati, Ohio, United States, 45249

Sponsors and Collaborators

Sanofi Pasteur, a Sanofi Company

Investigators

• Study Director: Medical Director; Sanofi Pasteur Inc.

More Information

Additional Information:

Related Info  Related Info 

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT02563093
• Other Study ID Numbers: GRC57; U1111-1161-2491 ( Other Identifier: WHO )
• First Posted: September 29, 2015
• Results First Posted: December 12, 2016
• Last Update Posted: December 12, 2016
• Last Verified: October 2016

Keywords provided by Sanofi ( Sanofi Pasteur, a Sanofi Company ):

Influenza; Fluzone® Quadrivalent, Influenza Vaccine; Fluzone® Intradermal Quadrivalent, Influenza Vaccine; Fluzone® High Dose, Influenza Vaccine

Additional relevant MeSH terms:

Influenza, Human; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Vaccines; Immunologic Factors; Physiological Effects of Drugs